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The role of PKA and PKCε pathways in prostaglandin E 2 ‐mediated hypernociception
Author(s) -
Sachs D,
Villarreal CF,
Cunha FQ,
Parada CA,
Ferreira SH
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2008.00093.x
Subject(s) - protein kinase c , chemistry , nociception , protein kinase a , adenylyl cyclase , prostaglandin e2 , hyperalgesia , pharmacology , agonist , prostaglandin e , prostaglandin , endocrinology , medicine , signal transduction , receptor , kinase , biochemistry
Background and purpose: Protein kinase (PK) A and the ε isoform of PKC (PKCε) are involved in the development of hypernociception (increased sensitivity to noxious or innocuous stimuli) in several animal models of acute and persistent inflammatory pain. The present study evaluated the contribution of PKA and PKCε to the development of prostaglandin E 2 (PGE 2 )‐induced mechanical hypernociception. Experimental approach: Prostaglandin E 2 ‐induced mechanical hypernociception was assessed by constant pressure rat paw test. The activation of PKA or PKCε was evaluated by radioactive enzymic assay in the dorsal root ganglia (DRG) of sensory neurons from the hind paws. Key results: Hypernociception induced by PGE 2 (100 ng) by intraplantar (i.pl.) injection, was reduced by i.pl. treatment with inhibitors of PKA [A‐kinase‐anchoring protein St‐Ht31 inhibitor peptide (AKAPI)], PKCε (PKCεI) or adenylyl cyclase. PKA activity was essential in the early phase of the induction of hypernociception, whereas PKC activity was involved in the maintenance of the later phase of hypernociception. In the DRG (L4‐L5), activity of PKA increased at 30 min after injection of PGE 2 but PKC activity increased only after 180 min. Moreover, i.pl. injection of the catalytic subunit of PKA induced hypernociception which was markedly reduced by pretreatment with an inhibitor of PKCε, while the hypernociception induced by paw injection of PKCε agonist was not affected by an inhibitor of PKA (AKAPI). Conclusions and implications: Taken together, these findings are consistent with the suggestion that PKA activates PKCε, which is a novel mechanism of interaction between these kinases during the development of PGE 2 ‐induced mechanical hypernociception.